头孢硫脒等6种抗菌药物对革兰阳性球菌体外抗菌活性研究

目的对比研究头孢硫脒(CTM)、头孢唑啉(CEZ)、头孢呋辛(CXM)、头孢曲松(CTRX)、苯唑西林(OXL)、万古霉素(VCM)对99株临床分离G+球菌的体外抗菌活性.方法采用琼脂平板稀释法测定最低抑菌浓度(MIC).结果CTM对金黄色葡萄球菌的敏感率为97.06%,强于CTRX;CTM对表皮葡萄球菌的敏感率为91.67%,强于CTRX和OXL,对甲氧西林耐药的葡萄球菌(MRS)的抗菌作用明显优于CEZ、CXM、CTRX;CTM对粪肠球菌的抗菌活性与万古毒素相仿,强于CEX、CXM、CTRX、OXL.结论头孢硫脒对葡萄球菌和粪肠球菌具有很强的体外抗菌活性.     

头孢硫脒与奈替米星对90株革兰阳性球菌联合药敏研究

目的评价头孢硫脒与奈替米星对90株G+球菌体外联合抗菌效应.方法采用棋盘法设计,微量肉汤稀释法测定.测定不同浓度组合的三组抗菌药物对90株临床分离的G+球菌的最低抑菌浓度,并计算FIC指数.结果头孢硫脒对金黄色葡萄球菌、表皮葡萄球菌、粪肠球菌的MIC50分别为16mg/L、1mg/L、2mg/L,与奈替米星联合应用后,其MIC50分别显著的降低至0.5mg/L、0.125mg/L、0.25mg/L.FIC指数结果表明头孢硫脒与奈替米星抗菌药物联合应用,对金黄色葡萄球菌、表皮葡萄球菌、粪肠球菌多数呈协同和相加作用,并以协同作用为主(66.7%～90%),无关作用较少(0～6.6%),无拮抗作用.结论头孢硫脒与奈替米星联合应用对90株G+球菌呈基本协同或相加作用.     

头孢硫脒与奈替米星对90株革兰阳性球菌联合药敏研究

目的:评价头孢硫脒与奈替米星对90株G+球菌体外联合抗菌效应.方法:采用棋盘法设计,微量肉汤稀释法测定.测定不同浓度组合的三组抗菌药物对90株临床分离的G+球菌的最低抑菌浓度,并计算FIC指数.结果:头孢硫脒对金黄色葡萄球菌、表皮葡萄球菌、粪肠球菌的MIC50分别为16mg/L、1mg/L、2mg/L,与奈替米星联合应用后,其MIC50分别显著的降低至0.5mg/L、0.125mg/L、0.25mg/L.FIC指数结果表明头孢硫脒与奈替米星抗菌药物联合应用,对金黄色葡萄球菌、表皮葡萄球菌、粪肠球菌多数呈协同和相加作用,并以协同作用为主(66.7%～90%),无关作用较少(0～6.6%),无拮抗作用.结论:头孢硫脒与奈替米星联合应用对90株G+球菌呈基本协同或相加作用.     

头孢硫脒等抗菌药物对革兰氏阳性球菌体外抗菌活性研究

目的 评价头孢硫脒及其他12种抗菌药对革兰氏阳性球菌的体外抗菌活性。方法 从本院2001年9月～12月临床病人血液、痰、分泌物、尿标本中分离出57株致病菌，经VITEK—AMS分析仪鉴定，共有金葡球菌24株，凝固酶阴性葡萄菌21株，粪肠球菌12株。质控金葡球菌ATCC25923，粪肠球菌ATCC29212。判断标准按2000年NCCLS标准。结果 头孢硫脒等10种抗菌药对金葡球菌体外抗菌活性，头孢硫脒敏感率87．5％，有2株耐药菌(8．33％)，敏感率与万古霉素、利福平比较无统计意义(P＞0．05)。头孢硫脒等10种抗菌药对凝固酶阴性葡萄球菌体外抗菌活性，头孢硫脒敏感率85．7％，有3株耐药菌株(14．29％)，敏感率略低于万古霉素、利福平(P＞0．05)，显著高于庆大霉素、氧氛沙星等(P＜0．05)。对粪肠球菌，头孢硫脒敏感率83．33％，有2株耐药菌株(16．67％)，其敏感率与庆大霉素、四环素、链霉素差异显著(P＜0．005，P＜0．01)。结论头孢硫脒是临床治疗金葡球菌、凝固酶阴性葡萄球菌、粪肠球菌感染的有效药物。     

头孢硫脒最低抑菌浓度及其影响因素研究

目的评价头孢硫脒对近年来中国临床分离致病菌的体外最低抑菌浓度(MIC)及影响因素。方法以琼脂二倍稀释法对794株临床分离致病菌进行了MIC测定。比较细菌接种量、培养基pH、培养基血清蛋白含量改变后对头孢硫脒MIC值的影响。结果头孢硫脒对苯唑西林敏感金黄色葡萄球菌(MSSA)和表皮葡萄球菌(MSSE)的MIC₉₀值分别为0.50,0.12 mg·L^-1;对青霉素敏感肺炎链球菌(PSSP)MIC₉₀值为0.12 mg·L^-1,对青霉素不敏感肺炎链球菌(PNSSP)MIC₉₀值≤1 mg·L^-1;对化脓性链球菌MIC₉₀值为8μg·L^-1;对氨苄西林敏感粪肠球菌和屎肠球菌MIC₉₀值分别为1,16 mg·L^-1。头孢硫脒对氨苄西林敏感嗜血杆菌属和卡他莫拉菌MIC₉₀值≤4 mg·L^-1。头孢硫脒对革兰氏阳性厌氧菌也有一定抗菌作用。以上因素对头孢硫脒抗菌活性基本无影响。结论头孢硫脒对包括肠球菌在内的革兰氏阳性菌具有较强的抗菌作用。     

69株革兰阳性球菌对抗菌药物的体外敏感度测定

目的了解抗菌药物对临床常见革兰阳性球菌的体外抗菌活性。方法采用K B法对临床分离得到的69株革兰阳性球菌进行药物敏感性测定。结果革兰阳性球菌对万古霉素的敏感率为100.0%，表皮葡萄球菌对头孢硫脒的敏感率为89.7%，对头孢唑林为84.4%;金黄色葡萄球菌对头孢硫脒的敏感率为95.0%，对头孢唑林为93.5%。肠球菌对头孢硫脒和头孢唑林的敏感率均为50%。结论头孢硫脒对革兰阳性球菌的抗菌活性优于头孢唑林、红霉素、阿奇霉素，仅次于万古霉素。头孢硫脒与头孢唑林对肠球菌的抗菌活性基本相同。     

莫西沙星对224株肠球菌的体外抗菌活性研究

目的观察莫西沙星对224株肠球菌的体外抗菌活性。方法采用二倍琼脂稀释法对224株肠球菌进行体外抗菌实验．并与意大利Aventis公司生产的替考拉宁和Lilly公司生产的万古霉素进行抗菌效果对比。结果莫西沙星的抗菌效果较好，对169株粪肠球菌和51株屎肠球菌的MIC90均为4mg／L，替考拉宁和万古霉素对169株粪肠球菌的MIC90分别为1、2mg／L；对51株屎肠球菌的MIC90分别为0．5和2mg／L。结论莫西沙星对224株肠球菌的抗菌效果较好，肠球菌对莫西沙星的敏感率均为76．34％。莫西沙星的抗菌效果低于替考拉宁和万古霉素。     

头孢硫脒与环丙沙星对革兰阳性球菌的联合药敏研究

目的　评价头孢硫脒 /环丙沙星对于临床分离的金黄色葡萄球菌(包括耐甲氧西林金葡菌)、表皮葡萄球菌 (包括耐甲氧西林表葡菌)、粪肠球菌的体外联合抗菌效应。方法采用棋盘法设计,微量肉汤稀释法测定。测定不同浓度组合的抗菌药物对 90株临床分离的革兰阳性球菌的最低抑菌浓度,并计算FIC指数判定联合效应。结果　头孢硫脒 /环丙沙星联合应用后,其MIC50明显降低。FIC≤0 5占 53 3% ~93 3%; 0 52为 0。结论　环丙沙星与头孢硫脒联合用药对革兰阳性球菌主要表现为协同作用。     

国产头孢硫脒对224株凝固酶阴性葡萄球菌的体外抗菌活性研究

目的观察头孢硫脒对表皮葡萄球菌、溶血葡萄球菌等凝固酶阴性葡萄球菌的体外抗菌活性。方法采用琼脂稀释法对头孢硫脒进行224株表皮葡萄球菌、溶血葡萄球菌等凝固酶阴性葡萄球菌的最低抑菌浓度(MIC)测定。结果头孢硫脒对100株耐甲氧西林的凝固酶阴性葡萄球菌和124株甲氧西林敏感的凝固酶阴性葡萄球菌的MIC50,MIC90分别为0．5、128、≤0．125和2μg／ml。对甲氧西林敏感的表皮葡萄球菌(MSSE)、溶血葡萄球菌(MSSH)和里昂葡萄球菌(MSSL)的MIC90分别为0．5、2．0和2．0μg／ml。结论头孢硫脒对124株甲氧西林敏感的凝固酶阴性葡萄球菌具有较强的抑菌力。     

利福霉素等6种抗菌药物对金葡球菌体外抗菌作用比较研究

目的 比较利福霉素、甲氧西林、氟氧头孢、美洛培南、奈替米星、万古霉素对mecA基因阳性和mecA基因阴性的金葡球菌的体外抗菌活性。方法 采用多重PCR方法检测金葡球菌的mecA基因携带情况,采用平皿二倍稀释法进行6种抗菌药物的最低抑菌浓度的测定。结果 6种抗菌药物对mecA 基因阴性的金葡球菌的MIC50和MIC90分别为甲氧西林（2、4mg/L), 利福霉素（0．125、0．25mg/L）,氟氧头孢（0．5、2mg/L）,美洛培南（0．25、0．25mg/L）,奈替米星（2、2mg/L）,万古霉素（2．2mg/L）。对mecA基因阳性的金葡球菌的MIC50和MIC90分别为甲氧西林（＞256、＞256mg/L),利福霉素（0．031、0．031mg/L）,氟氧头隐(32、64mg/L）,美洛培南（64、128mg/L）、奈替米星（32、64mg/L）,万古霉素（4、4mg/L）。结论 6种抗菌药物对mecA基因阴性的金葡球菌均有很强的体外抗菌活性,但对mecA基因阳性且对甲氧西林耐药的金葡球菌,氟氧头孢、美洛培南和奈替米星的体外抗菌活性差,万古霉素和利福霉素具有很强的体外抗菌活性,特别是利福霉素对于MRSS的抗菌活性明显强于MSSA。     

Synthesis,Cytotoxicity and Antileishmanial Activity of Some N-(2-(indol-3-yl)ethyl)-7-chloroquinolin-4-amines

We report herein the condensation of 4,7-dichloroquinoline (1) with tryptamine (2) and D-tryptophan methyl ester (3) . Hydrolysis of the methyl ester adduct (5) yielded the free acid (6) . The compounds were evaluated in vitro for activity against four different species of Leishmania promastigote forms and for cytotoxic activity against Kb and Vero cells. Compound (5) showed good activity against the Leishmania species tested, while all three compounds displayed moderate activity in both Kb and Vero cells.     

Lung disease and PKCs

The lung offers a rich opportunity for development of therapeutic strategies focused on isozymes of protein kinase C (PKCs). PKCs are important in many cellular responses in the lung, and existing therapies for pulmonary disorders are inadequate. The lung poses unique challenges as it interfaces with air and blood, contains a pulmonary and systemic circulation, and consists of many cell types. Key structures are bronchial and pulmonary vessels, branching airways, and distal air sacs defined by alveolar walls containing capillaries and interstitial space. The cellular composition of each vessel, airway, and alveolar wall is heterogeneous. Injurious environmental stimuli signal through PKCs and cause a variety of disorders. Edema formation and pulmonary hypertension (PHTN) result from derangements in endothelial, smooth muscle (SM), and/or adventitial fibroblast cell phenotype. Asthma, chronic obstructive pulmonary disease (COPD), and lung cancer are characterized by distinctive pathological changes in airway epithelial, SM, and mucous-generating cells. Acute and chronic pneumonitis and fibrosis occur in the alveolar space and interstitium with type 2 pneumocytes and interstitial fibroblasts/myofibroblasts playing a prominent role. At each site, inflammatory, immune, and vascular progenitor cells contribute to the injury and repair process. Many strategies have been used to investigate PKCs in lung injury. Isolated organ preparations and whole animal studies are powerful approaches especially when genetically engineered mice are used. More analysis of PKC isozymes in normal and diseased human lung tissue and cells is needed to complement this work. Since opposing or counter-regulatory effects of selected PKCs in the same cell or tissue have been found, it may be desirable to target more than one PKC isozyme and potentially in different directions. Because multiple signaling pathways contribute to the key cellular responses important in lung biology, therapeutic strategies targeting PKCs may be more effective if combined with inhibitors of other pathways for additive or synergistic effect. Mechanisms that regulate PKC activity, including phosphorylation and interaction with isozyme-specific binding proteins, are also potential therapeutic targets. Key isotypes of PKC involved in lung pathophysiology are summarized and current and evolving therapeutic approaches to target them are identified.     

Gender-related symptoms and correlates of alcohol dependence among men and women with a lifetime diagnosis of alcohol use disorders

This study explored gender-related symptoms and correlates of alcohol dependence in a crosssectional study of 150 men and 150 women with a lifetime diagnosis of alcohol use disorders (AUD). Participants were recruited in equal numbers from treatment settings, correctional centres and the general community. Standardized measures were used to determine participants' use of substances, history of psychiatric disorders and psychosocial stress, their sensation seeking and family history of substance use and mental health disorders. Multivariate analyses were used to detect patterns of variables associated with gender and the lifetime severity of AUD. Men had a longer history of severe AUD than women. Women had similar levels of alcohol dependence and medical and psychological sequelae as men, despite 6 fewer years of AUD. More women than men had a history of severe psychosocial stress, severe dependence on other substances and antecedent mental health problems, especially mood and anxiety disorders. There were differences in family history of alcohol-related problems approximating same-gender aggregation. The severity of a lifetime AUD was predicted by its earlier age at onset and the occurrence of other disorders, especially anxiety, among both men and women. The limitations in the generalizability of these findings due to sample idiosyncrasies are discussed.     

Biochemical and molecular characterisation of cubozoan protein toxins

Class Cubozoa includes several species of box jellyfish that are harmful to humans. The venoms of box jellyfish are stored and discharged by nematocysts and contain a variety of bioactive proteins that are cytolytic, cytotoxic, inflammatory or lethal. Although cubozoan venoms generally share similar biological activities, the diverse range and severity of effects caused by different species indicate that their venoms vary in protein composition, activity and potency. To date, few individual venom proteins have been thoroughly characterised, however, accumulating evidence suggests that cubozoan jellyfish produce at least one group of homologous bioactive proteins that are labile, basic, haemolytic and similar in molecular mass (42-46 kDa). The novel box jellyfish toxins are also potentially lethal and the cause of cutaneous pain, inflammation and necrosis, similar to that observed in envenomed humans. Secondary structure analysis and remote protein homology predictions suggest that the box jellyfish toxins may act as α-pore-forming toxins. However, more research is required to elucidate their structures and investigate their mechanism(s) of action. The biological, biochemical and molecular characteristics of cubozoan venoms and their bioactive protein components are reviewed, with particular focus on cubozoan cytolysins and the newly emerging family of box jellyfish toxins.     

Dose tolerability of chronically inhaled voriconazole solution in rodents

Invasive pulmonary aspergillosis (IPA) is a fungal disease of the lung associated with high mortality rates in immunosuppressed patients despite treatment. Targeted drug delivery of aqueous voriconazole solutions has been shown in previous studies to produce high tissue and plasma drug concentrations as well as improved survival in a murine model of IPA. In the present study, rats were exposed to 20 min nebulizations of normal saline (control group) or aerosolized aqueous solutions of voriconazole at 15.625 mg (low dose group) or 31.25 mg (high dose group). Peak voriconazole concentrations in rat lung tissue and plasma after 3 days of twice daily dosing in the high dose group were 0.85 ± 0.63 μg/g wet lung weight and 0.58 ± 0.30 μg/mL, with low dose group lung and plasma concentrations of 0.38 ± 0.01 μg/g wet lung weight and 0.09 ± 0.06 μg/mL, respectively. Trough plasma concentrations were low but demonstrated some drug accumulation over 21 days of inhaled voriconazole administered twice daily. Following multiple inhaled doses, statistically significant but clinically irrelevant abnormalities in laboratory values were observed. Histopathology also revealed an increase in the number of alveolar macrophages but without inflammation or ulceration of the airway, interstitial changes, or edema. Inhaled voriconazole was well tolerated in a rat model of drug inhalation.